Although inflammatory responses to microbes by helper T (Th) cells, such as Th1, Th2, and Th17 cells, in the gut are essential for host defense against invading pathogens, aberrant effector responses can cause disruption of tissue homeostasis. Therefore, a balance between inflammatory responses and immunological tolerance is elaborately regulated by Foxp3⁺ regulatory (Treg) cells through several mechanisms. Patients with IPEX syndrome spontaneously develop colitis and autoimmune diseases caused by FOXP3 mutations that result in reduced suppressive activity of Foxp3⁺ Treg cells, which highlights the crucial role of Foxp3⁺ Treg cells in the maintenance of host physiology. The human intestinal tract contains a huge number of commensal bacteria. Accumulating evidence reveals that microbial components and metabolites are involved in maintenance of gut homeostasis through the induction of Foxp3⁺ Treg cells. Perturbations of the microbiota community, termed dysbiosis, are observed in patients with chronic inflammatory disorders, autoimmune diseases, and nervous system diseases. Therefore, further understanding of the mechanisms by which microbiota regulate the development and function of Foxp3⁺ Treg cells will help identify therapeutic targets and the subsequent development of therapeutic interventions in a variety of diseases.

Gut microbiota is involved in the induction and functional maturation of various immune cells. However, there are only a few immune mechanisms that directly regulate gut bacteria. Immunoglobulin A (IgA) is a major immune mechanism which is important for the regulation of microbiota. It has been known for a long time that gut microbiota is critically involved in the induction of IgA. Recently, with the development of next-generation sequencing technologies, it has gradually been revealed that IgA also plays an important role in the regulation of the composition and function of gut bacteria. In this review, we introduce recent findings on the factors involved in the interaction between IgA and microbiota.

To examine the defecation status of healthy adults ingesting foods (FF16) containing 35 strains of 16 species of lactic acid bacteria and bifidobacteria and their usefulness for the intestinal flora, we conducted a randomized, double-blind, crossover-controlled trial including 20 healthy adults. Subjects were 41-61 years old with 3-5 bowel movements per week. Subjects who took the test diet containing FF16 (150 mg/day) showed statistically significant improvements in the overall score of the Japanese Constipation Rating Scale, frequency of defecation, anal pain during defecation, and defecation status compared to before the intervention. In the test food intake group, Bacteroidaceae, Sutterellaceae, and Oscillospiraceae, noxious bacteria related to stool odor, were statistically significantly reduced compared to the placebo group. In addition, Desulfovibrionaceae, Peptostreptococcaceae, Rikenellaceae, Eggerthellaceae and Actinomycetaceae, beneficial bacteria involved in the reduction of infectious diseases, were statistically significantly increased compared to the placebo group. From these facts, improvement of intestinal flora was confirmed. The above results confirm that ingestion of FF16 is effective at improving defecation status and is accompanied by changes in intestinal bacterial flora.